In vitro expanded human CD4+CD25+ regulatory T cells suppress effector T cell proliferation.

Regulatory T cells (Tregs) have been shown to be critical in the balance between autoimmunity and tolerance and have been implicated in several human autoimmune diseases. However, the small number of Tregs in peripheral blood limits their therapeutic potential. Therefore, we developed a protocol that would allow for the expansion of Tregs while retaining their suppressive activity. We isolated CD4+CD25 hi cells from human peripheral blood and expanded them in vitro in the presence of anti-CD3 and anti-CD28 magnetic Xcyte Dynabeads and high concentrations of exogenous Interleukin (IL)-2. Tregs were effectively expanded up to 200-fold while maintaining surface expression of CD25 and other markers of Tregs: CD62L, HLA-DR, CCR6, and FOXP3. The expanded Tregs suppressed proliferation and cytokine secretion of responder PBMCs in co-cultures stimulated with anti-CD3 or alloantigen. Treg expansion is a critical first step before consideration of Tregs as a therapeutic intervention in patients with autoimmune or graft-versus-host disease

An Optimized Round-Robin Scheduling of Speakers for Peers-to-Peers-Based Byzantine Faulty Tolerance

© 2018 IEEE. Blockchain technology has been showing its strong performance on decentralized security when integrating with Internet of Things network. However, the trilemma of scalability-security-decentralization exists in Blockchain-based IoT. Therein the typical round-robin scheduling implemented in the Byzantine Faulty Tolerance (BFT) proposed by Neo's Blockchain has a significant delay when consecutive faulty miners exist. This paper proposes a novel analysis model for evaluating the network performance collapse in general, followed by an optimized round-robin scheduling for the case when the mutual latency difference is not significant enough for ranking. Based on the model, the optimized mechanism is able to increase the block rate for a specific subset of consecutive faulty miners by nearly 50% and provide a linearly positive growth rate of the mitigation with respect to the fail rate of a single miner, which strongly promotes the efficiency of the P2P-based BFT consensus algorithm

Low-Temperature-Induced Controllable Transversal Shell Growth of NaLnF4 Nanocrystals

Highly controllable anisotropic shell growth is essential for further engineering the function and properties of lanthanide-doped luminescence nanocrystals, especially in some of the advanced applications such as multi-mode bioimaging, security coding and three-dimensional (3D) display. However, the understanding of the transversal shell growth mechanism is still limited today, because the shell growth direction is impacted by multiple complex factors, such as the anisotropy of surface ligand-binding energy, anisotropic core–shell lattice mismatch, the size of cores and varied shell crystalline stability. Herein, we report a highly controlled transversal shell growth method for hexagonal sodium rare-earth tetrafluoride (β-NaLnF4) nanocrystals. Exploiting the relationship between reaction temperature and shell growth direction, we found that the shell growth direction could be tuned from longitudinal to transversal by decreasing the reaction temperature from 310 °C to 280 °C. In addition to the reaction temperature, we also discussed the roles of other factors in the transversal shell growth of nanocrystals. A suitable core size and a relative lower shell precursor concentration could promote transversal shell growth, although different shell hosts played a minor role in changing the shell growth direction

Fabrication and characterisation of nanoscale Ni-CGO electrode from nanocomposite powders

Incorporating nanoparticles into SOC electrode is a viable method to improve the electrochemical performance. In this work, nanoparticles of NiO and gadolinia-doped ceria (CGO) approximately 10 nm in diameter fabricated using a continuous hydrothermal flow synthesis are made into nano-structured SOC fuel electrodes via mixing and co-sintering. Both the Ni and CGO are of 50-100 nm in diameter in the final electrode. FIB-SEM 3-D tomography is carried out on the nanoscale Ni-CGO electrode which has been aged for 70 h, showing a high active triple phase boundary density of 3 µm-2 and a high active double phase boundary density of 2 µm-1. The total polarisation resistance of the electrode is stable at 0.20 Ω cm2 under open circuit conditions at 800 °C annealing in humidified 5% H2-N2

Dynamic Covalent Synthesis of Crystalline Porous Graphitic Frameworks

Porous graphitic framework (PGF) is a two-dimensional (2D) material that has emerging energy applications. An archetype contains stacked 2D layers, the structure of which features a fully annulated aromatic skeleton with embedded heteroatoms and periodic pores. Due to the lack of a rational approach in establishing in-plane order under mild synthetic conditions, the structural integrity of PGF has remained elusive and ultimately limited its material performance. Here, we report the discovery of the unusual dynamic character of the C=N bonds in the aromatic pyrazine ring system under basic aqueous conditions, which enables the successful synthesis of a crystalline porous nitrogenous graphitic framework with remarkable in-plane order, as evidenced by powder X-ray diffraction studies and direct visualization using high-resolution transmission electron microscopy. The crystalline framework displays superior performance as a cathode material for lithium-ion batteries, outperforming the amorphous counterparts in terms of capacity and cycle stability. Insertion of well-defined, evenly spaced nanoscale pores into the two-dimensional (2D) layers of graphene invokes exciting properties due to the modulation of its electronic band gaps and surface functionalities. A bottom-up synthesis approach to such porous graphitic frameworks (PGFs) is appealing but also remains a great challenge. The current methods of building covalent organic frameworks rely on a small collection of thermodynamically reversible reactions. Such reactions are, however, inadequate in generating a fully annulated aromatic skeleton in PGFs. With the discovery of dynamic pyrazine formation, we succeeded in applying this linking chemistry to obtain a crystalline PGF material, which has displayed high electrical conductivity and remarkable performance as a cathode material for lithium-ion batteries. We envision that the demonstrated success will open the door to a wide array of fully annulated 2D porous frameworks, which hold immense potential for clean energy applications. We report the unusual dynamic characteristics of the C=N bonds in the pyrazine ring promoted under basic aqueous conditions, which enables the successful synthesis of two-dimensional porous graphitic frameworks (PGFs) featuring fully annulated aromatic skeletons and periodic pores. The PGF displayed high electrical conductivity and remarkable performance as a cathode material for lithium-ion batteries, far outperforming the amorphous counterparts in terms of capacity and cycle stability

A Unified Analytical model for proof-of-X schemes

© 2020 Nakamoto protocol, practically solving the Byzantine Generals Problem, can support a variety of proof-based consensus engines, referred to as Proof-of-X (PoX) in permissionless Blockchains. However, there has been to date in lack of a general approach for each miner to evaluate its steady-state profit against the competitors. This paper presents a Markov model which captures explicitly the weighted resource distribution of PoX schemes in large-scale networks and unifies the analysis of different PoX schemes. The new model leads to the development of three new unified metrics for the evaluation, namely, Resource Sensitivity, System Convergence, and Resource Fairness, accounting for security, stability, and fairness, respectively. The generality and applicability of our model are validated by simulation results, revealing that among typically non-Fairness-oriented PoX schemes (such as Proof-of-Work (PoW) and Proof-of-Stake (PoS)), the strongly restricted coinage-based PoS with a Pareto-distributed resource can offer the best performance on Resource Sensitivity, while Proof-of-Publication (PoP) with normal-distributed resource performs the best on System Convergence. Our simulations also reveal the important role of carefully designed Resource Fairness parameter in balancing Resource Sensitivity and System Convergence and improving the performance compared with other non-Fairness-oriented PoX schemes

Iterative positive solutions for singular nonlinear fractional differential equation with integral boundary conditions

In this article, we study the existence of iterative positive solutions for a class of singular nonlinear fractional differential equations with Riemann-Stieltjes integral boundary conditions, where the nonlinear term may be singular both for time and space variables. By using the properties of the Green function and the fixed point theorem of mixed monotone operators in cones we obtain some results on the existence and uniqueness of positive solutions. We also construct successively some sequences for approximating the unique solution. Our results include the multipoint boundary problems and integral boundary problems as special cases, and we also extend and improve many known results including singular and non-singular cases

Independent external validation of the QRISK3 cardiovascular disease risk prediction model using UK Biobank

Objective To externally evaluate the performance of QRISK3 for predicting 10 year risk of cardiovascular disease (CVD) in the UK Biobank cohort. Methods We used data from the UK Biobank, a large-scale prospective cohort study of 403 370 participants aged 40–69 years recruited between 2006 and 2010 in the UK. We included participants with no previous history of CVD or statin treatment and defined the outcome to be the first occurrence of coronary heart disease, ischaemic stroke or transient ischaemic attack, derived from linked hospital inpatient records and death registrations. Results Our study population included 233 233 women and 170 137 men, with 9295 and 13 028 incident CVD events, respectively. Overall, QRISK3 had moderate discrimination for UK Biobank participants (Harrell’s C-statistic 0.722 in women and 0.697 in men) and discrimination declined by age (<0.62 in all participants aged 65 years or older). QRISK3 systematically overpredicted CVD risk in UK Biobank, particularly in older participants, by as much as 20%. Conclusions QRISK3 had moderate overall discrimination in UK Biobank, which was best in younger participants. The observed CVD risk for UK Biobank participants was lower than that predicted by QRISK3, particularly for older participants. It may be necessary to recalibrate QRISK3 or use an alternate model in studies that require accurate CVD risk prediction in UK Biobank

In situ valence modification of Pd/NiO nano-catalysts in supercritical water towards toluene oxidation

Noble metals, e.g. Pd, are often made into hybrid or composite catalysts (with less expensive materials) to oxidize industry-source emitted volatile organic compounds (VOCs) at low temperatures. In general, the loadings of these metals should be optimized to reduce costs whilst maintaining activity. There exists the possibility to obtain highly active catalysts with low loadings of noble metals by properly tuning the valence state of the metal(s). However, the relationship between the valence state and its effect on catalyst performance is still a matter of debate. In this article, we used supercritical water (sc-H2O), in the presence of oxidizing or reducing gases, as a feasible reaction medium to synthesize Pd/NiO hybrid nano-catalysts and in situ modify the valence state of Pd. After subjecting the catalysts to a range of analytical techniques, including XRD, H2-TPR, DRIFT, TPSR, etc., we unveiled that Pd0 is more active than PdOx and metal oxides in the catalytic oxidation of toluene. This is mainly because the stabilized Pd0 is capable of activating gaseous oxygen (and toluene) at low temperatures and returning to the original state by toluene even with excess oxygen. Although PdOx could desorb active oxygen under a reducing atmosphere and might assist in the oxygen spillover from NiO, it is difficult to convert into Pd0 in an oxygen-rich environment. The developed Pd0-dominated catalyst was found to be robust and highly active after an ageing test with and without water vapour

Survey: Sharding in Blockchains

© 2013 IEEE. The Blockchain technology, featured with its decentralized tamper-resistance based on a Peer-to-Peer network, has been widely applied in financial applications, and even further been extended to industrial applications. However, the weak scalability of traditional Blockchain technology severely affects the wide adoption due to the well-known trillema of decentralization-security-scalability in Blockchains. In regards to this issue, a number of solutions have been proposed, targeting to boost the scalability while preserving the decentralization and security. They range from modifying the on-chain data structure and consensus algorithms to adding the off-chain technologies. Therein, one of the most practical methods to achieve horizontal scalability along with the increasing network size is sharding, by partitioning network into multiple shards so that the overhead of duplicating communication, storage, and computation in each full node can be avoided. This paper presents a survey focusing on sharding in Blockchains in a systematic and comprehensive way. We provide detailed comparison and quantitative evaluation of major sharding mechanisms, along with our insights analyzing the features and restrictions of the existing solutions. We also provide theoretical upper-bound of the throughput for each considered sharding mechanism. The remaining challenges and future research directions are also reviewed